Introduction: Previous in vitro and in vivo studies demonstrate protective properties of kissorphin (KSO) peptides against amyloid-β (Aβ) neurotoxicity1,2. Overexpression of the KiSS-1 gene, that encodes the KSO peptides, is also neuroprotective1,3. Endocannabinoids and KSO peptides are neuroprotective against Aβ 25-35, but not Aβ 31-35 peptides1,4. The KiSS-1 gene expression is regulated by endocannabinoids5. The aim of this study was to determine whether endocannabinoids contribute to KSO protection against Aβ toxicity using a CB1 cannabinoid receptor antagonist.